U.S. patent application number 15/017351 was filed with the patent office on 2018-04-26 for devices and methods for treatment of heart failure by splanchnic nerve ablation.
The applicant listed for this patent is Axon Therapies, Inc.. Invention is credited to Mark GELFAND, Howard LEVIN.
Application Number | 20180110561 15/017351 |
Document ID | / |
Family ID | 61971134 |
Filed Date | 2018-04-26 |
United States Patent
Application |
20180110561 |
Kind Code |
A1 |
LEVIN; Howard ; et
al. |
April 26, 2018 |
DEVICES AND METHODS FOR TREATMENT OF HEART FAILURE BY SPLANCHNIC
NERVE ABLATION
Abstract
A method for treating a heart failure patient by ablating a
nerve of the splanchnic sympathetic nervous system to increase
venous capacitance and reduce pulmonary blood pressure. A method
including: inserting a catheter into a vein adjacent the nerve,
applying stimulation energy and observing hemodynamic effects,
applying ablation energy and observing hemodynamic effects,
applying simulation energy after the ablation and observing
hemodynamic effects.
Inventors: |
LEVIN; Howard; (Teaneck,
NJ) ; GELFAND; Mark; (New York, NY) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Axon Therapies, Inc. |
New York |
NY |
US |
|
|
Family ID: |
61971134 |
Appl. No.: |
15/017351 |
Filed: |
February 5, 2016 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
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62112395 |
Feb 5, 2015 |
|
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62162266 |
May 15, 2015 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61N 1/00 20130101; A61B
2018/00791 20130101; A61B 2018/00214 20130101; A61B 2018/00875
20130101; A61B 2018/00863 20130101; A61B 18/1492 20130101; A61B
2090/064 20160201; A61B 2018/00404 20130101; A61B 2018/00434
20130101; A61N 1/36017 20130101 |
International
Class: |
A61B 18/14 20060101
A61B018/14 |
Claims
1. A method for improving heart function in a human patient with
heart failure or with symptoms associated with heart failure,
comprising: positioning an endovascular catheter comprising a
proximal region, a flexible shaft, and a distal region, wherein the
flexible shaft connects the proximal and distal regions and is a
length sufficient to access the abdominal vasculature of the
patient relative to an access location, wherein the proximal region
is configured to remain external to the patient, and wherein the
distal region is configured to be advanced through the patient
vasculature and dimensioned to terminate in the abdominal
vasculature in contact with the inner wall of a vein and comprises
at least one ablation element, at least one stimulation element,
and at least one detection element; advancing the distal region
through patient vasculature; application of at least one ablation
element; and removing the endovascular catheter from the
patient.
2. A method for improving heart function in a mammalian patient
with heart failure or with symptoms associated with heart failure,
comprising: positioning an endovascular catheter comprising a
proximal region, a flexible shaft, and a distal region, wherein the
flexible shaft connects the proximal and distal regions and is a
length sufficient to access the abdominal vasculature of the
patient relative to an access location, wherein the proximal region
is configured to remain external to the patient, and wherein the
distal region is configured to be advanced through the patient
vasculature and dimensioned to terminate in the abdominal
vasculature in contact with the inner wall of a vein and comprises
at least one ablation element, at least one stimulation element,
and at least one detection element; advancing the distal region
through patient vasculature, application of at least one ablation
element; and removing the endovascular catheter from the
patient.
3. The method of claim 1, wherein the advancing step further
comprises confirming positioning success.
4. The method of claim 1, wherein the application step further
comprises confirmation of an ablation of a nerve.
5. The method of claim 1, wherein the proximal region comprises an
energy source and a controller with embedded logic and
software.
6. The method of claim 1, wherein the proximal region comprises an
energy source and a controller with embedded logic and software,
and further comprises a user interface.
7. The method of claim 1, wherein every ablation element is
associated with at least one stimulation element.
8. The method of claim 1, wherein the distal region further
comprises a detection element chosen from the group comprising of
systemic, pulmonary arterial and venous pressure transducers, at
least one cardiac output detector, at least one blood flow monitor,
or combinations thereof.
9. The method of claim 1, wherein the distal region further
comprises a detection element and at least one other detection
element positioned in a different part of the circulation
system.
10. The method of claim 1, wherein the ablation element is chosen
from the list consisting of an electrode, cryo console, drug
delivery device, injection of neurolytic blocking agent, ultrasound
device, radio frequency device, thermal ablation device, laser
emitter and any combination thereof
11. The method of claim 10, wherein the radio frequency device
outputs an electrical current having a frequency in a range of 350
to 500 kHz and a power in a range of 5 to 50 W.
12. The method of claim 1, wherein the detection element is a blood
pressure transducers.
13. The method of claim 1, wherein the detection element is a
tissue temperature sensor.
14. The method of claim 1, wherein the detection element is a
hemodynamic sensor.
15. The method of claim 1, wherein the detection element is an
environmental temperature sensor.
16. The method of claim 1, wherein the detection element is a
tissue impedance sensor
17. The method of claim 1, wherein the distal region comprises a
deployable structure chosen from the list consisting of a balloon,
a cage, a basket, a preformed shape, lasso and loop and any
combination thereof
18. The method of claim 1, wherein the access location is a radial,
brachial, subclavian, jugular or femoral veins.
19. The method of claim 1, wherein the positioning step is
proceeded by the introduction and advancement of a guide-wire to
facilitate advancement of a catheter through patient
vasculature.
20. The method of claim 1, wherein the abdominal vasculature are
small veins.
21. The method of claim 1, wherein the abdominal vasculature are
small intrathoracic veins.
22. The method of claim 1, wherein the abdominal vasculature is an
azygos vein.
23. The method of claim 1, wherein the abdominal vasculature is a
hemiazygos vein.
24. The method of claim 1, wherein the abdominal vasculature is an
intercoastal vein.
25. The method of claim 1, wherein the ablation element and
stimulation element are positioned on the catheter relative to one
another so that the area in which the stimulation signal delivered
by the stimulation element correlates with an ablation zone in
which ablation energy delivered by the ablation element is
sufficient to cause irreversible ablation of nerve tissue.
26. The method of claim 1, wherein the catheter may be configured
to sterile, elongated, flexible, irrigated, sheathed, deflectable,
radio florescent, radio opaque, or any combination thereof.
27. The method of claim 1, wherein the confirming the positioning
the distal region is performed by an automated algorithmic process
to confirm a change in at least one selected hemodynamic or
physiological parameter.
28. The method of claim 27, comprising selecting electrode or
electrode pair, recording a baseline of the hemodynamic parameter,
delivering stimulation pulse with a current (I), a pulse width
(pw), a frequency (F) and a duty cycle (D) in about I=0-10 mA,
pw=100-1000 us, F=20-40 Hz, D=50% pulsing between 20-60 s,
recording the selected hemodynamic parameter.
29. The method of claim 28, further comprising determining if the
selected hemodynamic parameter is >20% from baseline, allowing
parameter to return to baseline and repeating for at least three
measurement, recording average measurements for at least 3
stimulations, and if standard error is within +/-10%, confirming
the change in the selected parameter.
30. The method of claim 27, wherein the hemodynamic or
physiological parameter is selected from the group of responses
consisting of pupil dilation, increased sweating, increased heart
rate, increased blood pressure, increased mean arterial pressure
and any combination thereof.
31. A method for improving heart function in a human patient with
heart failure or with symptoms associated with heart failure,
comprising: positioning an endovascular catheter comprising a
proximal region, a flexible shaft, and a distal region, wherein the
flexible shaft connects the proximal and distal regions and is a
length sufficient to access the abdominal vasculature of the
patient relative to an access location, wherein the proximal region
is configured to remain external to the patient, and wherein the
distal region is configured to be advanced through the patient
vasculature and dimensioned to terminate in the abdominal
vasculature in contact with the inner wall of a vein adjacent a
target nerve and comprises at least one ablation element, at least
one stimulation element, and at least one detection element;
advancing the distal region through patient vasculature, applying
electrical stimulating to inner wall of a vein to sufficient to
stimulate the adjacent nerve detecting physiological changes to
confirm positioning success application of at least one ablation
element; re-applying electrical stimulating to inner wall of a vein
previously sufficient to stimulate the adjacent nerve to confirm
irreversible ablation of target nerve; and removing the
endovascular catheter from the patient.
32. The method of claim 31 further comprising re-positioning distal
region and repeating electrical stimulation until positioning is
confirmed.
33. A method comprising determining that an electrode on a catheter
in an intercostal vein of a live mammalian patient is proximate a
target nerve in the patient by detecting a change in at least one
selected hemodynamic parameter or physiological parameter of the
patient while the electrode applies electrical energy to the
intercostal vein.
34. The method of claim 33, wherein the electrode is one of a
plurality of electrodes on the catheter and the method further
comprises applying electrical energy to the intercostal vein
sequentially from each of the electrodes and selecting at least one
of the electrodes which, when applying the electrical energy,
causes a change to the at least one selected hemodynamic parameter
or physiological parameter.
35. The method of claim 34 further comprising recording a baseline
of the selected hemodynamic or physiological parameter while the
electrodes do not apply electrical energy to the intercostal vein,
delivering at least one stimulation pulse sequentially to each of
the electrodes, wherein the stimulation pulse has a current (I) of
0 to 10 mA, a pulse width (pw) of 100 to 1000 us, a frequency (F)
of 20 to 40 Hertz and a duty cycle (D) of 20 to 60 seconds,
recording a values of the selected hemodynamic or physiological
parameter in response to each stimulation pulse, and correlating
the recorded value to the electrode applying the electrical energy
while the value was recorded.
36. The method of claim 35, further comprising, for each sequential
application, determining if the value for selected hemodynamic or
physiological parameter is greater than a threshold from the
baseline, allowing the selected hemodynamic or physiological
parameter to return to or near the baseline and repeat for at least
three measurement, recording average measurements for at least 3
stimulations, and if standard error is within +/-10%, confirming
the change in the selected parameter.
37. The method of claim 33, wherein the hemodynamic or
physiological parameter is selected from the group of responses
consisting of pupil dilation, increased sweating, increased heart
rate, increased blood pressure, increased mean arterial pressure
and any combination thereof.
Description
RELATED APPLICATIONS
[0001] This application claims the benefit of U.S. Provisional
Patent Applications 62/112,395 filed Feb. 5, 2015, and 62/162,266,
filed May 15, 2015, the entirety of both these applications is
incorporated by reference.
BACKGROUND
[0002] Heart failure (HF) is a medical condition that occurs when
the heart is unable to pump sufficiently to sustain the organs of
the body. Heart failure is a serious condition and affects millions
of patients in the United States and around the world.
[0003] In the United States alone, about 5.1 million people suffer
from heart failure and according to the Center for Disease Control,
the condition costs the nation over $30 billion in care,
treatments, medications, and lost production.
[0004] The normal healthy heart is a muscular pump that is, on
average, slightly larger than a fist. It pumps blood continuously
through the circulatory system to supply the body with oxygenated
blood. Under conditions of heart failure, the weakened heart cannot
supply the body with enough blood and results in cardiomyopathy
(heart muscle disease) characterized by fatigue and shortness of
breath, making even everyday activities such as walking very
difficult.
[0005] Oftentimes, in an attempt compensate for this dysfunction,
the heart and body undergo physiological changes that temporarily
mask the inability of the heart to sustain the body. These changes
include the enlargement of heart chamber, increased cardiac
musculature, increased heart rate, raised blood pressure, poor
blood flow, and imbalance of body fluids in the limbs and
lungs.
[0006] One common measure of heart health is left ventricular
ejection fraction (LVEF) or ejection fraction. By definition, the
volume of blood within a ventricle immediately before a contraction
is known as the end-diastolic volume (EDV). Likewise, the volume of
blood left in a ventricle at the end of contraction is end-
systolic volume (ESV). The difference between EDV and ESV is stroke
volume (SV). SV describes the volume of blood ejected from the
right and left ventricles with each heartbeat. Ejection fraction
(EF) is the fraction of the EDV that is ejected with each beat;
that is, it is SV divided by EDV. Cardiac output (CO) is defined as
the volume of blood pumped per minute by each ventricle of the
heart. CO is equal to SV times the heart rate (HR).
[0007] Cardiomyopathy, in which the heart muscle becomes weakened,
stretched, or exhibits other structural problems, can be further
categorized into systolic and diastolic dysfunction based on
ventricular ejection fraction.
[0008] Systolic dysfunction is characterized by a decrease in
myocardial contractility. A reduction in the LVEF results when
myocardial contractility is decreased throughout the left
ventricle. CO is maintained in two ways: left ventricular
enlargement results in a higher SV and an increase in contractility
as a result of the increased mechanical advantage from stretching
the heart. However, these compensatory mechanisms are eventually
exceeded by continued weakening of the heart and CO decreases,
resulting in the physiologic manifestations of HF. The left side of
the heart cannot pump with enough force to push a sufficient amount
of blood into the systemic circulation. This leads to fluid backing
up into the lungs and pulmonary congestion. In general terms,
systolic dysfunction is defined as an LVEF less than 40% and heart
failure in these patients can be broadly categorized as heart
failure with reduced ejection fraction (HFrEF).
[0009] Diastolic dysfunction refers to cardiac dysfunction in which
left ventricular filling is abnormal and is accompanied by elevated
filling pressures. In diastole, while the heart muscle is relaxed
the filling of the left ventricle is a passive process that depends
on the compliance (defined by volume changes over pressure
changes), or distensibility, of the myocardium or heart muscle.
When the ventricles are unable to relax and fill, the myocardium
may strengthen in an effort to compensate to poor SV. This
subsequent muscle hypertrophy leads to even further inadequate
filling. Diastolic dysfunction may lead to edema or fluid
accumulation, especially in the feet, ankles, and legs.
Furthermore, some patients may also have pulmonary congestion as
result of fluid buildup in the lungs. For patients with HF but
without systolic dysfunction, diastolic dysfunction is the presumed
cause. Diastolic dysfunction is characteristic of not only HCM,
which is characterized by the thickening of heart muscle, but also
RCM, which is characterized by rigid heart muscle that cannot
stretch to accommodate passive filling. In general terms, diastolic
dysfunction is defined as a LVEF of greater than 40% and HF in
these patients can be broadly categorized as heart failure with
preserved ejection fraction (HFpEF).
[0010] While a number of drug therapies successfully target
systolic dysfunction and HFrEF, for the large group of patients
with diastolic dysfunction and HFpEF no promising therapies have
yet been identified. The clinical course for patients with both
HFrEF and HFpEF is significant for recurrent presentations of acute
decompensated heart failure (ADHF) with symptoms of dyspnea,
decreased exercise capacity, peripheral edema etc. Recurrent
admissions for ADHF utilize a large part of current health care
resources and could continue to generate enormous costs.
[0011] While the pathophysiology of HF is becoming increasingly
better understood, modern medicine has, thus far, failed to develop
new therapies for chronic management of HF or recurrent ADHF
episodes. Over the past few decades, strategies of ADHF management
and prevention have and continue to focus on the classical paradigm
that salt and fluid retention is the cause of intravascular fluid
expansion and cardiac decompensation. Increasing evidence suggests
that fluid homeostasis and control of intravascular fluid
distribution is disrupted in patients with HF. Disregulation of
this key cardiovascular regulatory component could not only explain
findings in chronic HF but also in ADHF. Consequently, blocking of
the autonomic nervous system to alter fluid distribution in the
human body could be used as a therapeutic intervention.
[0012] Additionally, the classical understanding of HF
pathophysiology emphasizes the mechanism of poor forward flow
(i.e., low CO), resulting in neurohumoral, or sympathetic nervous
system (SNS) up-regulation. However, new evidence emphasizes the
concurrent role of backward failure (i.e., systemic congestion) in
the pathophysiology and disease progression of HF. Coexisting renal
dysfunction with diuretic resistance often complicates the
treatment of HF and occurs more frequently in patients with
increased cardiac filling pressures. Chronic congestive heart
failure (CHF) is characterized by longstanding venous congestion
and increased neurohumoral activation. Critically important has
been the identification of the splanchnic vascular bed as a major
contributor to blood pooling and cardiac physiology. Newly evolving
methods and devices involving sympathetic nervous system blocking
and manipulation of systems including the splanchnic vascular bed
have opened novel avenues to approach the treatment of heart
disease. In particular, the role of sympathetic nerves that
innervate smooth muscle in the walls of splanchnic veins have
become better known. In the case of hyperactivity of these nerves
they became a novel target in the treatment of CHF.
SUMMARY OF THE INVENTION
[0013] In view of the foregoing, it would be desirable to provide
an apparatus and methods to affect neurohumoral activation for the
treatment of HF and particularly diastolic HF, (HFpEF).
[0014] The present invention may be used to provide an improved
treatment option for patients suffering from HF by ablating the
splanchnic nerves (e.g., greater, lesser and least) that innervate
organs and vasculature of the abdominal compartment and the greater
splanchnic nerve (GSN) in particular. By selectively ablating
specific nerves, the invention provides a novel method and device
that can affect circulating blood volume, pressure, blood flow and
overall heart and circulatory system functions. In this way, the
present invention helps to introduce novel solutions to treat HF
and particularly HFpEF based on the most contemporary physiological
theories regarding HF.
[0015] About 5% of the total body water is located within the
vasculature in the form of blood. The venous system contains
approximately 70% of total blood volume and is roughly 30 times
more compliant than the arterial system. Venous compliance is a
measure of the ability of a hollow organ or vessel to distend and
increase in volume with increasing internal pressure. A number of
mechanisms are involved in regulation of volume, most importantly
the neurohormonal system. On the arterial side, flow and resistance
are regulated by resistance vessels. The sympathetic nervous system
plays a major role in determining systemic vascular resistance
(SVR) predominantly through activation and deactivation of
cardiopulmonary and arterial baroreflexes, as well as through
changes in circulating norepinephrine.
[0016] Capacitance is a determinant of the venous vascular function
and higher vascular capacitance means more blood can be stored in
the respective vasculature. The autonomic nervous system is the
main regulatory mechanism of vascular capacitance.
[0017] Circulating blood is distributed into two physiologically
but not anatomically separate compartments: the "venous reservoir"
and "effective circulatory volume". The term "venous reservoir" (or
"unstressed volume") refers to the blood volume that resides mainly
in the splanchnic vascular bed and does not contribute to the
effective circulating volume. The venous reservoir that is also
referred to as "unstressed volume" or "vascular capacitance" can be
recruited through a number of mechanisms like activation of the
sympathetic nervous system, drugs, or hormones.
[0018] The term "effective circulatory volume" (or "stressed
volume") refers to blood that is present mainly in the arterial
system and in non-splanchnic venous vessels and is one of the main
determinants of preload of the heart. The stressed blood volume and
systemic blood pressure are regulated by the autonomic nervous
system of which the sympathetic nervous system is a part.
[0019] The unstressed volume of blood is mostly contained in the
splanchnic reservoir or "splanchnic vascular bed". The splanchnic
reservoir consists of vasculature of the visceral organs including
the liver, spleen, small and large bowel, stomach, as well as the
pancreas. Due to the low vascular resistance and high capacitance
the splanchnic vascular bed receives about 25% of the CO and the
splanchnic veins contain anywhere from 20% to 50% of the total
blood volume.
[0020] Consequently, the splanchnic vascular bed serves as the
major blood reservoir, which can take up or release, actively and
passively, the major part of any change in circulating blood
volume.
[0021] While experimenting with cadavers and animals inventors made
two important discoveries: (a) venous reservoir can be artificially
manipulated and modified by selectively ablating or stimulating the
GSN, and (b) in humans and some animals the GSN, although hidden
deep in the body, can be accessed very closely from superficial
veins, through the venous system, and the azygos veins.
[0022] Splanchnic veins are considerably more compliant than veins
of the extremities. Animal and human studies demonstrate that the
splanchnic reservoir can not only store considerable amounts of
blood, but blood can also be actively or passively recruited from
it into the systemic circulation in response to variations of the
venous return of blood to the heart and physiologic need for heart
preload. One of the main determinants of active recruitment is
sympathetic nerve activity (SNA), which through hormones and a
neurotransmitters epinephrine and norepinephrine causes
venoconstriction, thereby reducing splanchnic capacitance and
increasing effective circulatory volume. This can be explained by a
large numbers of adrenergic receptors in the splanchnic vasculature
that are sensitive to changes to the sympathetic nervous system.
Compared with arteries, splanchnic veins contain more than five (5)
times the density of adrenergic terminals. The consequence is a
more pronounced venous vasomotor response in the splanchnic system
compared to other vascular regions.
[0023] The splanchnic vascular bed is well suited to accommodate
and store large amounts of blood as well as shift blood back into
active circulation, naturally acting in a temporary blood volume
storage capacity. The high vascular capacitance allows the
splanchnic vascular bed to maintain preload of the heart and
consequently arterial blood pressure and CO over a wide range of
total body volume changes. Once the storage capacity of the
splanchnic vascular bed is reached, increases in total body fluid
express themselves as increased cardiac preload beyond physiologic
need and eventually extravascular edema and particularly fluid
accumulation in the lungs that is a symptom common in HF.
[0024] Increased activation of the sympathetic nervous system (SNS)
and the neurohormonal activation along with increases in body
fluids and salts have long been debated as causes versus effects of
HF. It has been previously suggested that in HF redistribution of
the splanchnic reservoir, driven by increased SNA to the splanchnic
vascular bed leading to decreased venous compliance and
capacitance, is responsible for increased intra-cardiac filling
pressure (preload) in the absence of increases in total body salt
and water. HF is marked by chronic over-activity of the SNS and the
neurohormonal axis. It is now suggested that SNA and neurohormonal
activation result in an increased vascular tone and consequently in
decreased vascular capacitance of the splanchnic vascular bed.
While peripheral vascular capacitance is mostly unchanged in HFpEF
and HFrEF compared to controls, the vascular capacitance of the
splanchnic vascular can be significantly decreased.
[0025] So-called "acute HF" is initiated by a combination of two
pathways: cardiac and vascular. The "cardiac pathway" is generally
initiated by a low cardiac contractility reserve, while the
"vascular pathway" is common to acute HF (AHF) that exhibits mild
to moderate decrease in cardiac contractility reserve.
[0026] In ADHF, which is characterized by worsening of the
symptoms: typically shortness of breath (dyspnea), edema, and
fatigue, in a patient with existing heart disease, the cardiac
filling pressures generally start to increase more than 5 days
preceding an admission. While this could reflect a state of
effective venous congestion following a build-up of volume, nearly
50% of patients gain only an insignificant amount of weight (<1
kg) during the week before admission. This means that in about 50%
of cases, decompensated HF is not caused by externally added fluid,
but rather symptoms and signs of congestion can be entirely
explained by redistribution of the existing intravascular
volume.
[0027] Acute increases in sympathetic nervous tone due to a variety
of known triggers like cardiac ischemia, arrhythmias, inflammatory
activity and psychogenic stress and other unknown triggers can
disrupt the body's balance and lead to a fluid shift from the
splanchnic venous reservoir into the effective circulation. This
results ultimately in an increase in preload and venous congestion.
This explains the finding that in ADHF in both HFrEF and HFpEF was
preceded by a significant increase in diastolic blood
pressures.
[0028] In many patients with HFpEF relatively small increases in
diastolic pressures/preload can result in decompensation due to
impaired relaxation of the ventricles. Thus patients with HFpEF are
more sensitive to intrinsic or extrinsic fluid shifts.
[0029] Chronic CHF is characterized by longstanding venous
congestion and increased neurohumoral activation. Like in acute
heart failure, the splanchnic vascular bed has been identified as a
major contributor to HF pathophysiology. Chronic decrease in
vascular compliance and capacitance makes the human body more
susceptible to recurrent acute decompensations, making significant
the consequences of chronic congestion of the splanchnic
compartment. While the splanchnic vascular compartment is well
suited to accommodate acute fluid shifts (e.g. change of posture to
orthostasis, exercise and dietary intake of water), the regulation
of the splanchnic vascular bed becomes maladaptive in chronic
disease states associated with increased total body volume and
increased splanchnic vascular pressure.
[0030] Clinically observed effects of HF drug regimens like
nitroglycerin and ACE inhibitors exhibit their positive effects in
the treatment of HF in part through an increase in splanchnic
capacitance subsequently shifting blood into the venous reservoir
thereby lowering left ventricular diastolic pressure.
[0031] An orthostatic stress test (tilt test) can help to
distinguish low vascular capacitance from normal. Orthostatic
stress causes blood shifts from the stressed volume into the
unstressed volume. Veins of the extremities are less compliant than
splanchnic veins, and therefore, their role as blood volume
reservoir is relatively minimal. Less known is that during body
tilt or standing up blood goes mostly into the splanchnic
compartment, which results in a decreased preload to the right and
left heart. Stimulation of the atrial and carotid baroreceptors
results in an increased sympathetic tone causing splanchnic
vasoconstriction. This compensatory mechanism is important, as it
can rapidly shift volume from the unstressed compartment into
active circulation. The hemodynamic response to tilt in chronic HF
is atypical, as there is no significant peripheral pooling in the
upright posture. It is assumed that the reduced capacitance of the
splanchnic compartment serves as a marker of sympathetic tone to
the splanchnic vasculature.
[0032] Acute oral or intravenous fluid challenge can also serve as
a test of splanchnic vascular capacitance. The vascular capacitance
determines how "full" the unstressed volume reservoir (venous
reservoir) is and how much more fluid can be taken up to it in
order to buffer the increase in effective circulation (stressed
volume). A fluid challenge could test the capacitance by measuring
the effects of a fluid bolus given via an I.V. infusion on cardiac
filling pressures.
[0033] Patients with a "full tank", (low capacitance of venous
reservoir), will not be able to buffer the hemodynamic effects of
the fluid bolus as well as patients with a high capacitance in the
venous reservoir. This will manifest in a bigger blood pressure
increase for the same added volume. Thus patients with HF, HFpEF
and patients with increased SNA will be more likely to respond to
the fluid challenge with a disproportional rise in cardiac filling
pressures. This could serve as a patient selection tool as well as
measure of therapeutic success.
[0034] To target the splanchnic nerves, primarily the greater
splanchnic nerve (GSN) and the thoracic sympathetic trunk and
celiac plexus, several invasive and minimally-invasive methods can
be used. Although not limited to these methods, access can be
transthoracic, transabdominal, percutaneous, transvascular or
transvenous. Transvascular access utilizes both vessels of the
venous and arterial system, while a transvenous method accesses the
nerve structures through the venous network of the cardiovascular
system and is envisioned in at least the following vessels:
azygos/hemiazygos vein, intercostal veins, vena cava, adrenal vein,
phrenic vein, and portal vein.
[0035] Tools for catheter navigation include use of extravascular
landmarks such as intercostal space and/or vertebrae. Internal
scans or detection methods may include fluoroscopic detection of
radiographic landmarks, CT scans, Mill and/or ultrasound. These
scans would be used for direct nerve visualization, or
visualization of adjacent vascular (e.g. azygos) and non-vascular
structures (diaphragm, vertebrae, ribs). The use of radiocontrast
and a guide wire can aid in the placement of the ablation element
of the device.
[0036] At the targeted site, some proposed methods of target
modulation, specifically to ablate a target nerve include cryo or
high temperature based ablation, local drug delivery (e.g. local
injection and infiltration by neurolitics, sympatholytics,
neurotoxins), local anesthetics, or energy delivery that could
include radio frequency (RF) ablation, ultrasound energy delivery,
or mechanical compression.
[0037] In light of the foregoing, it is desired that the present
invention provide treatment that is used in the cardiac
catheterization laboratory to ablate a splanchnic nerve such as a
greater splanchnic nerve unilaterally on the right or left side of
the body or bilaterally on both sides to mobilize blood out of the
effective circulation (stressed volume) and shift it into
splanchnic organs or vasculature, and splanchnic vascular bed
(venous reservoir) in order to moderately decrease and normalize
cardiac preload, reduce venous congestion, relieve pulmonary
congestion, reduce pulmonary blood pressures and thus sensation of
dyspnea and to increase or relatively maintain stroke volume,
enhance blood circulation and improve overall heart function. As
such, use of the present invention would grant patients suffering
from heart disease a return to a higher quality of living and may
prevent hospital admissions with ADHF.
[0038] Further, the present invention could be used in the therapy
of acute as well as chronic HF decompensation. Acute HF
decompensation would be prevented or its progression halted by an
offloading of the stressed volume and relieving venous congestion,
which is the main component of the renal dysfunction in HF. The
invention can be used in support of traditional medical therapy
like diuretics as it can interrupt or delay progression of cardiac
decompensation. Said offloading of the stressed volume and
relieving venous congestion can be expected to increase diuretic
responsiveness of the patients.
[0039] In a chronic CHF state, the invention can be used on a
long-term basis to improve fluid distribution, increase
capacitance, relieve venous congestion, improve relaxation of
ventricles and thus improve symptoms of congestion like shortness
of breath and improve exercise capacity.
[0040] Compared to present methods of nerve ablation, the invention
aims to create a reliable and consistent method of targeted
selective GSN ablation that is safe and causes no adverse effects
such as pain, serious long term damage to gastric function,
sensation or other unintended, untargeted nerve damage.
[0041] Additionally, the present invention fulfills a long desired
need to provide a treatment for HF, especially for patients of
diastolic or HFpEF and particularly a need to reduce pulmonary
artery blood pressure and relieve dyspnea (shortness of breath) in
response to exercise and in some cases at rest.
BRIEF DESCRIPTION OF THE DRAWINGS
[0042] Other advantages of this invention are made apparent in the
following descriptions taken in conjunction with the provided
drawings wherein are set forth, by way of illustration and example,
certain exemplary embodiments of the present invention wherein:
[0043] FIG. 1 is an anatomical representation of the supply of
sympathetic nerve fibers to organs of the human body.
[0044] FIG. 2 is a flow diagram showing the mechanisms of
decompensated heart failure
[0045] FIG. 3 is a partial flow diagram showing the role of
splanchnic compartment in blood volume distribution in heart
failure.
[0046] FIG. 4 is a partial flow diagram showing the role of the
therapeutic effects of invention to heart failure.
[0047] FIG. 5 is a graphical representation of pathophysiology of
acute decompensated heart failure.
[0048] FIG. 6 is an anatomical representation showing azygos vein
catheterization for right GSN ablation with an intravenous catheter
suitable for stimulation and ablation.
[0049] FIG. 7 is an anatomical representation showing the azygos
vein catheterization for left GSN ablation with an intravenous
catheter suitable for stimulation and ablation.
[0050] FIG. 8 is an anatomical representation showing the
hemiazygos vein catheterization for left GSN ablation with an
intravenous catheter suitable for stimulation and ablation.
[0051] FIG. 9 is an anatomical representation showing the
hemiazygos vein catheterization for right GSN ablation with an
intravenous catheter suitable for stimulation and ablation.
[0052] FIG. 10 is an anatomical representation showing left GSN
catheterization via the azygos vein to posterior intercostal
vein.
[0053] FIG. 11 is an anatomical representation showing the azygous
vein and greater splanchnic nerve and their proximity, which allows
for a transvenous approach with an intravenous catheter deployable
structure suitable for stimulation and ablation.
[0054] FIG. 12 is a plot of aortic and ventricular pressure in
response to electrical stimulation of a GSN in an animal study.
[0055] FIG. 13 shows a catheter suitable for stimulation and
ablation deployed in an intercostal vein in close proximity to the
GSN and sympathetic chain.
[0056] FIGS. 14A and 14B illustrate the different physiological
responses between stimulation of the sympathetic chain (FIG. 14A)
versus stimulation of the GSN (FIG. 14B).
[0057] FIG. 15 is a mapping algorithm used to determine an optimal
electrode pair that is based on in Mean Arterial Pressure (MAP)
levels recorded after a stimulus is delivered.
[0058] FIG. 16 is a plot of mean arterial pressure over time
showing response to stimulation of an ablated nerve.
[0059] FIG. 17 is a flowchart illustrating the steps from patient
selection to ablation therapy.
[0060] FIG. 18 is a schematic illustration of a distal end of an
ablation catheter.
[0061] FIGS. 19A to 19D are graphs illustrating responses of the
patient to the blocking of a nerve.
DETAILED DESCRIPTION OF THE INVENTION
[0062] The present invention relates to a medical device and method
that offers treatment of heart disease, dysfunction and heart
failure, particularly HFpEF through the mechanism of increased
venous capacitance and relief of pulmonary congestion and increased
diuretic responsiveness. This treatment is provided through
ablation of at least a portion of a splanchnic nerve (e.g., greater
splanchnic nerve or lesser splanchnic nerve) with a catheter
delivered to a vessel (e.g. azygos or hemiazygos vein or
intercostal vein) to impede or stop communication of a nerve signal
along the ablated nerve, which can affect physiological responses
that are directly or indirectly involved in the numerous factors of
cardiovascular health.
[0063] One preferred embodiment comprises a catheter delivered
through a patient's vascular system to an azygos or hemiazygos vein
and their branches for ablating a portion of a right or left
greater splanchnic nerve. The catheter may comprise an ablation
element (e.g., RF electrodes, cryogenic applicator, chemical agent
delivery needle, ultrasound transducer, laser emitter), and a means
to confirm proximity to target nerve, such as a greater splanchnic
nerve, or non-target neural structures (e.g., electrical
stimulation or blocking electrodes, cryogenic applicator, chemical
agent delivery needle, visual aids such as radiopaque or echogenic
markers). The catheter may be used as part of a system comprising
other components that contribute to the function of the catheter.
For example, the system may comprise an ablation energy source
(e.g., RF signal generator, cryo console, ultrasound signal
generator, chemical agent source or pump, laser generator), a
controller, or a computerized user interface. To ablate a portion
of a target nerve, the ablation energy source delivers ablation
energy from an ablation element positioned in a patient's blood
vessel (e.g. azygos, intercostal or hemiazygos vein) proximate the
target nerve. The ablation energy passes from the ablation element
to the target nerve. To confirm proximity to a target or non-target
neural structures a stimulating agent, such as electric field or a
drug known to activate sympathetic nerves, may be delivered to
temporarily activate or block nerve activity and a physiological
response may be observed or monitored for correlation to the nerve
stimulation or block. Similarly, success of ablation may be
confirmed by electric stimulation of the target nerve and observing
the physiologic response, changes in the physiologic response
compared to pre-ablation or absence of physiologic response where
one is expected.
[0064] Physiology
[0065] FIG. 1 is an anatomical representation of the supply of
sympathetic nerve fibers to organs of the human body. The SNS is
part of the autonomic nervous system, which also includes the
parasympathetic nervous system.
[0066] The SNS activates what is often termed the fight or flight
response. Like other parts of the nervous system, the sympathetic
nervous system operates through a series of interconnected neurons.
Sympathetic neurons are frequently considered part of the
peripheral nervous system, although there are many that lie within
the central nervous system.
[0067] Sympathetic neurons of the spinal cord (which is part of the
CNS) communicate with peripheral sympathetic neurons via a series
of sympathetic ganglia. Within the ganglia, spinal cord sympathetic
neurons join peripheral sympathetic neurons through chemical
synapses. Spinal cord sympathetic neurons are therefore called
presynaptic (or preganglionic) neurons, while peripheral
sympathetic neurons are called postsynaptic (or postganglionic)
neurons.
[0068] At synapses within the sympathetic ganglia, preganglionic
sympathetic neurons release acetylcholine, a chemical messenger
that binds and activates nicotinic acetylcholine receptors on
postganglionic neurons. In response to this stimulus,
postganglionic neurons principally release noradrenaline
(norepinephrine). Prolonged activation can elicit the release of
adrenaline from the adrenal medulla.
[0069] Once released, noradrenaline and adrenaline bind adrenergic
receptors on peripheral tissues. Binding to adrenergic receptors
causes the effects seen during the fight-or-flight response. These
include pupil dilation, increased sweating, increased heart rate,
and increased blood pressure.
[0070] Sympathetic nerves originate inside the vertebral column,
toward the middle of the spinal cord in the intermediolateral cell
column (or lateral horn), beginning at the first thoracic segment
of the spinal cord and are thought to extend to the second or third
lumbar segments. Because its cells begin in the thoracic and lumbar
regions of the spinal cord, the SNS is said to have a thoracolumbar
outflow. Thoracic splanchnic nerves (e.g., greater, lesser, or
least splanchnic nerves), which synapse in the prevertebral ganglia
are of particular interest for this invention.
[0071] FIG. 2 is a flow diagram showing the mechanisms of
decompensated heart failure. It illustrates the role of sympathetic
nerve activation in the mobilization of venous reservoir into the
effective circulatory volume leading to decompensation. Reversing,
at least partially, by ablation of a greater splanchnic nerve, the
sympathetic activation of splanchnic nerves is expected to relieve
HF symptoms and reduce load on the failing heart.
[0072] A particular area of interest in the body is the splanchnic
compartment, splanchnic vascular bed, or splanchnic reservoir,
which include the vasculature of the visceral organs including the
liver, spleen, small and large bowel, stomach as well as the
pancreas. The splanchnic venous vascular bed serves as the major
blood reservoir and can be affected by activation (e.g.,
stimulation) or deactivation (e.g., blocking or ablation) of
splanchnic nerves and particularly of the greater splanchnic nerve
(GSN) causing mobilization, release or uptake of venous blood from
or to splanchnic vascular beds, respectively, and important changes
in circulating blood volume.
[0073] The GSN may at least partially control splanchnic venous
capacitance. Capacitance is reduced in CHF patients and
particularly in some very hard to treat HFpEF patients as a part of
overall elevated sympathetic state. The sympathetic fibers in the
greater splanchnic nerve bundle that control contraction of
splanchnic veins are the particular target of the proposed ablation
therapy. In the context of this invention the GSN can mean right or
left greater splanchnic nerve and transvenous ablation and
stimulation can be performed from the azygos vein to access the
right greater splanchnic nerve, or from the hemiazygos vein to
access the left greater splanchnic nerve, or from their respective
tributaries (e.g. right or left intercostal veins) or a bilateral
treatment can be performed from both the azygos and hemiazygos to
access both right and left greater splanchnic nerves.
[0074] The splanchnic congestion and high venous pressure is
believed to adversely affect renal function and as illustrated by
hepatorenal syndrome that causes diuretic resistance. It is
believed by inventors that the proposed ablation may reverse this
phenomenon, improve renal function and enable diuretics to work
(restore diuretic responsiveness).
[0075] FIG. 3 and FIG. 4 show some of the interactions between
increases in sympathetic nervous system activity, including natural
firing of the GSN, and the storage of blood in the splanchnic bed.
As illustrated by FIG. 3, increased central SNA, can manifest, at
least partially, in the elevated activity of the GSN in all types
of HF, resulting in a lower splanchnic capacitance and possibly
stiffened, less-compliant splanchnic bed and regional effects
including a decrease in the amount of blood stored in the
splanchnic veins perfusing and surrounding the splanchnic organs
(e.g., liver, spleen, pancreas, stomach, bowels) and an increase in
the amount of blood in central veins. The volume of blood in
splanchnic veins or the splanchnic vascular bed can be described as
a "venous reservoir", or "unstressed volume" and refers to the
blood volume that does not contribute to the effective circulating
volume and is therefore hidden from circulation or the
hemodynamically hidden blood volume. The volume of blood in central
veins can be termed "effective circulatory volume" or "stressed
volume" and refers to blood that is present mainly in the
non-splanchnic veins and is one of the main determinants of preload
to the heart and in CHF can contribute to venous congestion, high
pulmonary circulation pressures and sensation of dyspnea.
[0076] Conversely, as illustrated by FIG. 4 the compliance of the
splanchnic bed can be relaxed or normalized from the "stiff" of
contracted state by decreased sympathetic nervous system activity.
Ablating a splanchnic nerve (e.g. GSN, lesser splanchnic nerve,
least splanchnic nerve) can result in a decrease of efferent
sympathetic tone to smooth muscle in the walls of veins in the
splanchnic vascular bed referred to as splanchnic "venodilation" or
in the overall decrease in sympathetic nervous system activity.
Understanding and utilizing these interactions are some of the
primary aims of several of the exemplary embodiments of the present
invention. Specifically, the capacitance of splanchnic vasculature
is desired to be increased.
[0077] FIG. 5 shows one possible clinical scenario in which the
sympathetic hyperactivity of the greater splanchnic nerve leads to
the acceleration of fluid overload and pulmonary venous congestion
in an HFpEF patient.
[0078] Endovascular Ablation
[0079] Endovascular nerve ablation, or ablation of neural
structures using a catheter delivered through a blood vessel,
particularly deep visceral nerves that are near the blood vessel
(e.g., less than about 5 mm from an internal vessel wall), may be
advantageous over surgical resection or ablation. For example,
endovascular ablation may be less invasive, be faster procedurally,
and have faster patient recovery. It may be beneficial to use a
patient's venous system to deliver ablation energy since
interventions in veins are considered safer than in arteries. Blood
pressure in a vein is lower and limits risk of bleeding and debris
or clot from ablation is safer since veins terminate in the lungs
that act as a natural blood filter. It is also advantageous that
veins are more elastic and can be occluded and stretched in order
to achieve better fixation and apposition of the ablating device in
relation to the nerve. Specifically, in the case of an azygos or
hemiazygos vein there is large redundancy in the venous system and
occlusion of the azygos vein is not dangerous to the patient.
[0080] There are several accepted methods of ablating a nerve
through a wall of a blood vessel such as RF ablation using
resistive heating, cryo-ablation using cold, ultrasound heating
ablation, and injection of neurolytic blocking agent (e.g., form of
nerve block involving the deliberate injury of a nerve by the
application of chemicals, in which case the procedure is called
"neurolysis") in which chemicals such as alcohol or more
specifically acting sympatholytic agents like guanethidine, botox
(i.e., botulinum toxin A) and others can be applicable.
[0081] A method and device for ablating a greater splanchnic nerve
using an ablation catheter placed in an azygos vein may be
configured to safely avoid important non-target nerves and
structures. For example, the celiac ganglion is near the greater
splanchnic nerve. Placement of an ablation element that creates,
for example, a 5 mm diameter lesion that permanently destroys the
GSN where it is in close proximity of the azygos vein at or
slightly above the diaphragm will protect the celiac ganglion from
ablation. Celiac ganglia are located in the abdominal cavity just
below the diaphragm. Other non-target nerves may include lesser and
least splanchnic nerves. Thus a targeted selective ablation of
nerves is possible to suite needs of different groups of patients
with HF.
[0082] FIG. 6 shows an example of a catheterization approach from a
left subclavian vein to a suitable position in an azygos vein for
right GSN ablation. FIG. 7 shows an example of a catheterization
approach from the left subclavian vein to a suitable position in a
hemiazygos vein for left GSN ablation by crossing over from azygos
to hemiazygos vein. Endovascular approaches to the azygos vein may
comprise introduction into the vascular system, for example, at the
radial, brachial, subclavian, jugular or femoral veins.
[0083] A guidewire may facilitate advancement of a catheter 10
through tortuous vessel pathways. The catheter may include an
extended tubular member 12 including lumens, such as for the
guidewire for injection of drugs and radiocontrast. Both bilateral
and unilateral, left and right GSN ablation is possible and may be
desired based on the patient's anatomy and responses to diagnostic
stimulation.
[0084] Approaches to identify the best location (mapping) and
target as well as the best approach to GSN ablation are shown in
FIGS. 8 and 9. These figures show examples of a catheterization
approach from a left subclavian vein to a suitable position in a
hemiazygos vein for left and right GSN ablation, respectively.
[0085] The catheters in FIGS. 6 to 10 may each comprise at least
one ablation element 14, 22 to deliver ablation therapy as well as
at least one electrical stimulation element to confirm proximity to
a target nerve, such as a GSN, or non-target neural structures. The
catheter in each of FIGS. 6 to 10 may be used as part of a system
comprising other components that contribute to the function of the
catheter. The system may comprise an ablation energy source 16
(e.g, RF signal generator, cryo console, ultrasound signal
generator, chemical agent source or pump, laser generator), an
electrical stimulation energy source and a computer controller 18
with embedded logic and software and a user interface with manual
controls and displays. A console 20 may house the ablation energy
source, the electrical stimulation energy source, the computer
controller, user interface and displays.
[0086] In an embodiment of the invention, as shown in FIG. 10,
ablation and stimulation elements on a catheter are positioned in
an intercostal vein near a GSN and sympathetic chain. The ablation
and stimulation elements can be electrodes.
[0087] The catheterization approach used in this example is the one
from a left subclavian vein via the azygous vein into the posterior
intercostal vein. Other approaches are possible through suitable
veins. The catheter may comprise at least one ablation element to
deliver ablation therapy and at least one electrical stimulation
element to confirm proximity to a target nerve, such as a GSN, or
non-target neural structures. The catheter may be used as part of a
system comprising other components that contribute to the function
of the catheter. The system may comprise an ablation energy source,
an electrical stimulation controller, or a user interface.
Additional elements such as monitoring of temperature and impedance
of tissue can be added to improve performance and safety of the
ablation system.
[0088] In an embodiment of the invention, as illustrated in FIG.
11, an ablation element on a catheter is positioned in an azygos
vein near a greater splanchnic nerve. The catheter may comprise a
deployable structure positioned at its distal region. The
deployable structure comprises at least one ablation element (e.g.,
RF electrode) that is placed in apposition with the azygos or
hemiazygos vein wall when the deployable structure is expanded. The
deployable structure may be a balloon, a cage, a basket, a
preformed shape such as a lasso or loop. The deployable structure
may further comprise at least one stimulation element 24 (e.g.,
electrical stimulation cathode and optionally anode), or a
visualization aid (e.g., radiopaque marker, contrast delivery
lumen). The azygos (and hemiazygos) veins which run up the right
and left sides of the thoracic vertebral column drain towards the
superior vena cava, in part within the thoracic cavity. Intravenous
access via the azygos vein allows for the catheter to access an
area in proximity to the thoracic splanchnic nerves, in particular,
the greater splanchnic nerve (GSN).
[0089] Experiments in animals and human cadavers where performed in
which the GSN was successfully accessed with a catheter advanced to
an azygos vein at the level of the diaphragm wherein an electrode
was positioned close enough to electrically stimulate and
potentially ablate the greater splanchnic nerve. In animals
experiments GSN access was performed on the right side. This was
confirmed by observing hemodynamic effects of greater splanchnic
nerve stimulation with electric pulses applied from the azygos
vein. Inventors also performed experiments where the GSN was
surgically accessed, visualized, stimulated with a nerve cuff and
later resected. Consistent and similar hemodynamic effects that
suggested therapeutic possibilities were observed.
[0090] Stimulation Confirmation Embodiments
[0091] Regardless of the modality of ablation, embodiments of a
device and method may further be configured to assist the ablation
procedure with a means to confirm safety and efficacy prior to and
following an ablation step. A means to confirm safety may comprise
detection of a non-target nerve or structure or absence thereof
within a range of ablation energy delivery. A means to confirm
technical efficacy may comprise detection of a target nerve within
range of ablation energy delivery before an ablation step and
absence of a target nerve signal transmission following the
ablation step. A means to confirm procedural efficacy may comprise
temporarily blocking a target nerve to assess if a resulting
physiologic response is representative of a desired clinical effect
of the procedure.
[0092] To facilitate a technically effective procedure, an
embodiment may involve confirming that the ablation lesion will be
created in a desired location and that a targeted nerve is
sufficiently within range of ablation energy delivery before
ablation energy is delivered to cause irreversible damage to the
target nerve or potentially to an untargeted area. This may be
achieved by delivering an electrical stimulating signal from at
least one stimulating electrode to excite nerves in proximity to
the stimulating electrode and observing a physiologic effect such
as hemodynamic changes. The stimulating electrodes may be a pair of
electrodes constituting an anode and cathode, a single monopolar
electrode communicating with a dispersive electrode, the same
component that is used to deliver an electrical ablation energy
such as radiofrequency or electroporation, or a distinct electrode
or pair of electrodes positioned appropriately relative to an
ablation element.
[0093] FIG. 12 illustrates a response to stimulation of a GSN at
the level just above the diaphragm in an animal experiment
performed by the inventors. The recognizable waveforms of aortic
and left ventricular pressure reflect the physiologic response to
stimulus. Similar increases were observed in central venous
pressure, right atrial pressure and pulmonary artery pressure that
can be measured and monitored in real time in any well-equipped
modern catheterization laboratory by a trained cardiologist.
[0094] In an embodiment wherein a stimulation electrode or pair of
electrodes is distinct from an ablation element they may be
positioned on the catheter relative to one another so that the
stimulation zone (e.g., region in which the stimulation signal
delivered by the stimulation electrode is strong enough to elicit
an action potential in a nerve) correlates with an ablation zone
(e.g., region in which ablation energy delivered by the ablation
element is sufficient to cause irreversible or long lasting damage
to nerve tissue).
[0095] A stimulation signal may be controlled by a computerized
console 20 (See FIG. 6-10) and may comprise a signal profile that
facilitates confirmation of technically efficacious positioning.
The computerized console may include processors accessing
non-transitory memory storing instructions that cause the console
to generate a stimulation signal. For example, the size of a
stimulation zone may be a function of amplitude and a signal
profile. The console may achieve the stimulation zone by delivering
signal energy by varying amplitude (e.g., linear ramp, stepwise
ramp, alternating levels) or frequency of stimulation. An observed
response corresponding to a given amplitude may indicate distance
of a target nerve to an ablation element, and delivery of ablation
energy may be adjusted (e.g., manually or automatically) to create
an efficacious ablation zone.
[0096] For example a different energy delivery electrode can be
selected or the catheter can be repositioned. In another example, a
signal profile comprises periods of on and off (e.g., stimulating
amplitude(s) and non-stimulating energy levels) in which a
physiologic response may follow the signal profile to eliminate
false positive or negative assessments.
[0097] In an embodiment, a transvenous application of electrical
stimulation of a nerve delivering currents of 0.5 to 15 mA,
frequency of 1 to 50 Hz and pulse duration of 50 to 500
microseconds may be suitable to test if proximity to the nerve is
within about 5 mm. Sedation may be used in order to prevent painful
sensation by the patient. If a physiologic response is elicited,
the cathode electrode is very likely to be within 1 to 5 mm
distance from the target nerve and ablation in that area is likely
to destroy the nerve permanently while sparing nerves outside of
the ablation zone in embodiments configured to create an ablation
zone of about 5 mm. It is estimated that the location closest to
the nerve and the corresponding electrode (See FIG. 13) will elicit
response at the lowest energy (example of nerve mapping). For
example, the ablation element may be an RF electrode (e.g., having
an exposed surface area of about 5 to 15 mm.sup.3) in monopolar
configuration with a dispersive grounding pad on the patient's skin
to complete the electrical circuit.
[0098] Ablation energy may be radiofrequency electrical current
having a frequency in a range of about 350 to 500 kHz and a power
in a range of about 5 to 50W.
[0099] The delivery of RF energy may be controlled by an energy
delivery module associated with the computer console that uses
temperature feedback from a sensor associated with the RF
electrode. Observation of a physiologic response may involve
equipment for measuring the response (e.g., equipment known in the
art for measuring or monitoring hemodynamic parameters such as
blood pressure and heart rate, or with sensors associated with the
catheter or the system) that provides an indication of the
parameter.
[0100] Confirmation of efficacious positioning may be assessed
manually by a practitioner by observing the parameter measurements
in real time. Alternatively confirmation may be assessed
automatically by the computerized system console that takes input
from the physiologic monitoring equipment and compares it to a
stimulation signal profile (automated mapping). The automated
mapping or confirmation assessment may further select or assist in
selecting an appropriate ablation energy delivery profile.
[0101] A catheter may be configured to monitor a physiologic
response to nerve stimulation and comprises a blood pressure
transducer on the catheter that may be positioned in a blood vessel
in addition to an ablation element and a stimulation element. The
device or system may further comprise a second blood pressure
transducer that may be positioned in a different part of the
circulation system (e.g., arterial system such as femoral or radial
artery, pulmonary circulation such as pulmonary artery, central
venous system such as vena cava or right atrium of the heart or
splanchnic circulation or pulmonary circulation system such as in a
pulmonary artery) to compare blood pressure measured in different
locations and assess changes in response to nerve stimulation.
[0102] To facilitate a safe procedure, an embodiment may involve
confirming that the ablation lesion will not do irreversible damage
to important non-target nerves, such as celiac ganglia or lesser
splanchnic nerve, if that is the selected therapy modality, before
ablation energy is delivered. This may be achieved by electrically
stimulating the adjacent nerves with the same or different
electrodes and observing the physiologic (e.g. heart rate or
hemodynamic such as blood pressure or flow) effects. An embodiment
may utilize the same principles and components as described above
wherein a stimulation zone is correlated to an ablation zone
however an observed physiologic response may be indicative that an
important non-target nerve is stimulated. An undesired response may
occur instead of or as well as a physiologic response from
stimulating a target nerve. In either case, a response from an
important non-target nerve may indicate that it is unsafe to ablate
as positioned. For example, an increase of central venous pressure
(CVP) or pulmonary artery pressure (PAP) can indicate the desired
response in combination with the reduction of Heart Rate (HR);
however, a concomitant increase in HR may indicate that an
important non-target nerve is within the stimulation zone and
associated ablation zone (e.g. nerve stimulating an adrenal gland)
and the ablation element and the associated stimulation element may
be repositioned and confirmation of safety and efficacy may be
reapplied. If both a target nerve and important non-target nerve
are stimulated by the same stimulation signal then the nerves may
be quite close together and delivering ablation energy may be
unsafe. To avoid risk of injuring the non-target nerve the ablation
element and stimulation element may be moved and stimulation
repeated until a position is found that is both safe and effective.
For example, the catheter can be advanced or different electrodes
selected on the catheter placed along the azygos, hemiazygos or
intercostal vein traveling along, crossing or traversing GSN and
sympathetic chain (See FIG. 13). Alternatively, a catheter may
comprise multiple ablation elements and corresponding stimulation
elements positioned along a length (e.g., about 1 to 5 cm) of a
distal segment of the catheter and stimulation regimens may be
delivered to select a position among the multiple positions that is
optimal.
[0103] Alternatively, a stimulation signal profile may narrow the
stimulation zone to identify an appropriate ablation setting that
would ablate the target nerve and not the non-target nerve. In
another embodiment a catheter may comprise a stimulation element
(e.g., at least one electrode or an electrode pair or pairs) having
a stimulation zone that spatially corresponds with an ablation
zone, and additionally have at least a second stimulation element
that is far enough away from the ablation element(s) that the
second stimulation zone corresponds to a region that is beyond the
ablation zone. In this embodiment a physiologic response elicited
by the second stimulation element and not the stimulation element
associated with the ablation element may indicate safe positioning.
In an embodiment wherein the ablation element is a cryo-ablation
element, a cryo- mapping technique may be applied to cool the area
and temporarily impede nerve conduction without permanently
destroying the nerves. For example, the cryo- mapping technique may
comprise delivering cryogenic energy from the cryo- ablation
element but with a duration or temperature that only temporarily
impedes nerve conduction. A physiologic response of a target nerve
or non-target nerve to temporarily impeded nerve conduction may be
different than a stimulated nerve. A temporarily impeded target
nerve may have a similar response as an ablated target nerve but
with a short duration.
[0104] FIG. 13 is an illustration of an endovascular catheter 30
including multiple ablation and stimulation elements 32. The
catheter is positioned in an intercostal vein via an azygous vein.
The ablation and stimulation elements 32 may be on the surface of
the catheter and positioned at regular increments along the length
of a distal end region of the catheter.
[0105] The distal segment of the catheter can be navigated into the
azygos and intercostal vein space of thoracic vertebrae T9, T10 or
T11 as illustrated by FIG. 10. The catheter is in close proximity
to both the GSN and the sympathetic chain. The diameter of the
catheter where electrodes are located can be 2-6 mm and almost
occluding and even possibly distending the intercostal vein. The
targeted nerve can be identified by using electrical stimulation of
the nerves along the catheter using selected electrodes as cathodes
and anodes and monitoring the physiological responses.
[0106] FIG. 14A and 14B are plots of the different physiological
responses observed during stimulation of the sympathetic chain and
GSN in animals, respectively. In an animal study, the left
sympathetic chain was stimulated via a catheter positioned in the
intercostal vein at the T6 level. The HR and MAP increased during
stimulation of the sympathetic chain as shown on FIG. 14A. The box
illustrates time of application of energy between 60 and 90 seconds
on X-axis. Changes in pulmonary artery pressure PAP and right
atrial pressure RAP confirm that the preload of the heart increased
in response to stimulation.
[0107] In a separate experiment the right GSN was selectively
stimulated using a cuff electrode placed on the thoracic section of
the GSN. Results are illustrated by FIG. 14B. During the GSN
stimulation period shown as a box, mean systolic pressure (MSP)
measured in the femoral artery increased while the HR decreased.
The reduction of HR was likely caused by the normal compensatory
response of the arterial baroreflex when the sudden upregulation of
heart stroke volume is detected. Inventors confirmed that while
blood flow in the inferior vena cava increased, cardiac output
remained relatively constant. The Ped trace on FIG. 14B illustrates
the increase of left ventricular end diastolic pressure (LVEDP) in
response to the mobilization of fluid from the venous reserve.
[0108] To facilitate a clinically effective procedure, an
embodiment may involve confirming that a patient will experience
the desired physiologic effect of ablation before delivering
ablation energy. This may be achieved by electrically,
pharmacologically or cryogenically blocking the nerve temporarily
and observing the physiologic response (e.g., hemodynamic effect).
Optionally, vascular nerve mapping or confirmation of technically
efficacious positioning as described herein to indicate that a
target nerve is within an ablation zone or confirmation of safe
positioning to indicate that an important non-target nerve is not
within the ablation zone may first be done, then a temporary nerve
block may be performed to assess potential clinical success. If
potential clinical success is assessed to have a physiologic
response as desired then ablation energy may be delivered to
produce a permanent or more long lasting clinical effect, which may
be analogous to the temporary clinical effect. Conversely, if the
physiologic response to temporary blocking is not as desired, a
physician may decide to not proceed with ablation. A different set
of stimulation and ablation elements may be chosen to apply
confirmation steps a different position may be found or the
procedure may be aborted.
[0109] To facilitate a technically and clinically effective
procedure, an embodiment may involve confirming that an ablation
was successful and that the target nerve no longer conducts signals
following delivery of ablation energy. This may be achieved by
delivering stimulation signals with the same or different
stimulation elements and observing the physiologic (e.g.
hemodynamic) effect.
[0110] Since the greater splanchnic nerve tracks along the azygos
vein for a considerable length, (e.g., up to about 3 to 5 cm), it
may be possible to stimulate the greater splanchnic nerve distal to
the ablation site and observe the absence of the hemodynamic
effect. A device configured to stimulate distal to an ablation site
may comprise a stimulation element having a stimulation zone
associated with an ablation zone and additionally, a stimulation
element positioned distal to the ablation element a sufficient
distance to be beyond the ablation zone.
[0111] An embodiment of a method for confirming that the relative
position of an ablation element to the target nerve (in this case a
greater splanchnic nerve) is safe and technically effective before
delivering ablation energy or selecting the appropriate ablation
element and corresponding stimulation elements from a group of
ablation and stimulation elements on a device may include the use
of a mapping algorithm.
[0112] The mapping algorithm, shown in FIG. 15 comprises the
following steps:
[0113] (i) Select electrode pairs (ideally below T10 and above
diaphragm or along the selected intercostal vein within 1-3 cm from
azygos or hemiazygos branching). It is understood that electrode
pairs refer to bipolar stimulation and ablation and one electrode
may be selected if ablation or stimulation is monopolar.
[0114] (ii) Record a selected hemodynamic parameter (e.g. MAP, CVP,
PAP, RAP) to establish the baseline. See, e.g., FIGS. 19A to 19D
before "GSN cut".
[0115] (iii) Deliver Stimulation pulse with Current (I), pulse
width (pw), frequency (F) and duty cycle (D) in about I=0-10 mA,
pw=100-1000 us, F=20-40 Hz, D=50% for 20-60 s. On and at least
20-60 s OFF. (See FIG. 16).
[0116] (iv) Record a selected hemodynamic parameter or parameters
(e.g. HR, MAP, CVP, PAP, RAP) such as shown in FIGS. 19A to 19D
after GSN cut.
[0117] (iv) If the selected hemodynamic parameter>20% from
baseline allow to return to baseline and possibly repeat.
[0118] Average measurements for 3 stimulations, for example, and if
standard error is within +/-10%, the change in the selected
hemodynamic parameter may be considered to be relevant.
[0119] Another method of confirming a suitable location for the
ablation and stimulation elements prior to delivering ablation
energy comprises a stimulation test in which a specific current,
frequency and pulse width are selected (e.g., manually or
automatically by a computerized algorithm) and stimulation is
performed between pairs of electrodes that are in contact with the
wall of the vessel (e.g., vein, azygos vein, hemiazygos vein). When
the electric field is sufficient to activate the GSN, a rapid rise
in Mean Arterial Pressure (MAP) or CVP or PAP and other hemodynamic
changes occurs within a few seconds and can be graphically recorded
and compared to assess ablation element placement.
[0120] A method of confirming technical success following delivery
of ablation energy, in other words confirming that a target nerve
has successfully been ablated may comprise the same or similar
electrical stimulation parameters delivered from the same
stimulation electrodes following ablation. Alternatively or
additionally electrical stimulation may be delivered from
stimulation electrodes positioned proximal to the location of an
ablation (closer to the brain or sympathetic chain) where a
physiologic response was elicited prior to ablating. Absence of
responses or significant attenuation of responses will indicate
technical success of the ablation.
[0121] To confirm this notion FIG. 16 illustrates an experiment
where the hemodynamic response to a greater splanchnic nerve
stimulation and block with locally injected lidocaine, a nerve
blocking agent, was tested in an animal. Time on the X-axis is in
minutes. The Y-axis represents arterial blood pressure in mmHg. The
first arrow from the left indicates the time of injection of
lidocaine. The second arrow indicates the time of application of
electrical stimulation to the greater splanchnic nerve proximal to
the blocked area of the nerve. The term "proximal" as used herein
with reference to a relative position on a nerve denotes a location
nearer to a point of origin, such as brain, spinal cord,
sympathetic chain or a midline of the body and where the term
"distal" is used to denote a location further away from the point
of origin and closer to the innervated peripheral organ such as
splanchnic vascular beds, liver and spleen. Following the first
stimulation proximal to the nerve block, no or very little
physiologic response is observed on arterial blood pressure, or
other physiologic parameters that are omitted on this graph for
simplicity. The third arrow illustrates electrical stimulation of
the greater splanchnic nerve for 30 seconds applied distal to the
lidocaine blocked area. The physiologic response manifests by
increase of mean arterial blood pressure and other hemodynamic
parameters as described in this application. This experiment,
performed using surgery, can be replicated using endovascular
ablation with the use of appropriate tools and advanced imaging.
Moving the stimulation electrode along the azygos vein, for
example, to points distal and proximal the ablation lesion can
confirm the effectiveness of ablation.
[0122] Alternatively switching between electrodes spaced along the
length of the catheter (See FIG. 13 for example) can be used. A
simple automation device can be envisioned to test different
electrode pairs and measure responses then creating a report on the
user interface.
[0123] Fluoroscopic imaging using body landmarks such as vertebrae,
heart, veins and the diaphragm can be used to facilitate
positioning of an ablation element or stimulation elements of a
catheter. If the nerve were unsuccessfully ablated, which may be
indicated by a positive hemodynamic change in response to
stimulation of the greater splanchnic nerve proximal the ablation,
then recourse may comprise ablation repeated at a higher energy
level, ablation repeated at a different location, or improved
electrode apposition.
[0124] It is noted that MAP monitoring as mentioned above is an
example and hemodynamic monitoring does not necessarily need to be
invasive monitoring and may be accomplished with a less invasive
monitoring of blood pressure, for example using a Nexfin or
ClearSight device (Edwards) for continuous monitoring of
hemodynamics commonly used in hospitals. The ClearSight system
quickly connects to the patient by wrapping an inflatable cuff
around the finger. The ClearSight system provides noninvasive
access to automatic, up-to-the-minute hemodynamic information
including: SV, CO, SVR, or Continuous Blood Pressure (cBP). Such a
monitoring device may be hooked up to a computerized console to
communicate physiologic response to the computer, which may
determine stimulation or ablation parameters based on the
physiologic responses.
[0125] An embodiment of a system of the present invention may
comprise an ablation catheter having at least one ablation element
(e.g., RF electrode) and at least one associated stimulation
element (e.g., stimulation electrode), a computerized console
configured to generate and control delivery of a stimulation signal
to the stimulation element, and a computerized console configured
to generate and control delivery of an ablation signal (e.g., RF
electrical current) to the ablation element. The stimulation
console and the ablation console may be separate machines or
integrated into one machine and may communicate to one another. The
system may further comprise components necessary to support the
type of ablation energy for example, if the ablation energy is RF
electrical current the system may further comprise a dispersive
grounding pad; if the ablation energy is a chemical agent the
system may further comprise a means to inject the agent such as a
manually operated syringe or automatically controlled pump. The
system may further comprise a hemodynamic monitoring device that is
in communication with the stimulation console or ablation console
to provide feedback of hemodynamic response to stimulation or
ablation. The computerized consoles may comprise algorithms that
facilitate analysis of stimulation and hemodynamic response. For
example, an algorithm may compute if a hemodynamic response to a
stimulation is significant based on time of response,
repeatability, difference from baseline.
[0126] In embodiments wherein an ablation catheter comprises
multiple ablation elements and associated stimulation elements, see
FIGS. 13 and 18, an algorithm may facilitate selection of an
optimal ablation element for example, based on strongest or
quickest response to stimulation, and then deliver ablation energy
to the selected ablation element. A console may comprise a
graphical user interface that provides intuitive graphics or
messages that help a user understand analysis of stimulation
response.
[0127] FIG. 17 is a chart that illustrates an example of patient
flow from patient selection to the execution of ablation of the GSN
to treat heart failure. One means for the selection of patients
suitable for GSN ablation may include evaluation of splanchnic
vascular capacitance. An orthostatic stress test (tilt table test),
fluid challenge, exercise test or an appropriate drug challenge can
help distinguish low vascular compliance from normal. Orthostatic
stress causes blood shifts from the stressed volume to the
unstressed volume. In healthy patients, to compensate for the
shift, sympathetic tone increases resulting in splanchnic
vasoconstriction and rapid mobilization of blood from the
unstressed compartment to the active circulation. The hemodynamic
response to tilt in chronic CHF is atypical, as there is not
significant peripheral pooling in the upright posture indicating
diminished splanchnic vascular capacitance. Acute oral or
intravenous fluid challenge is another test to assess splanchnic
vascular capacitance. A fluid challenge could test the capacitance
by measuring the effects of a fluid bolus on cardiac filling and
pulmonary pressures. Patients with low capacitance of the
splanchnic venous reservoir will be unable to compensate for the
hemodynamic effect of the fluid bolus. Patients with HF, HFPEF and
patients with increased SNA will be more likely to respond to the
fluid challenge with a disproportional rise in cardiac filing
pressure and other related and measurable physiologic parameters.
This response would indicate that the patient might be a candidate
for GSN ablation therapy. After patient identification as a
candidate for ablation therapy, the process of identifying the
appropriate nerve target is implemented as the first step in the
ablation procedure. Proper identification of the target nerve as
well as non-target nerves or structures within the range of the
ablative energy (mapping) is important to confirm the safety and
efficacy of the ablation procedure.
[0128] FIGS. 13 and 14 illustrate a means for using differences in
physiological responses to electrical stimulation to identify
target nerve (GSN) and a nearby non-target or different target
nerve (sympathetic chain). The choices of therapy can be made
selectively by the physician based on the mapping information and
the patient's individual responses and needs. For example an HFpEF
patient with high chronic HR or BP (hypertension) may require
different targeting than one with low blood pressure. After nerve
target identification and selection, one optional means of
confirmation of procedural efficacy is to temporarily block the
nerve target and evaluate whether the physiological response is
consistent with the desired clinical effect. After nerve target
identification has been confirmed, the non-target nerves or other
structures have been deemed outside of the range of ablation
energy, and procedural efficacy has been confirmed; ablation
therapy may be initiated.
[0129] Confirmation of the technical efficacy or success of the
ablation procedure may be accomplished by delivering electrical
stimulation proximal to the location of an ablation where a
physiological response was elicited prior to ablation. Absence or
attenuation of responses will indicate technical success of the
ablation procedure (see FIG. 16). Another means of confirming
technical efficacy may be evaluating splanchnic vascular
capacitance (tilt table and/or fluid challenge) and compare to
results before the procedure. If the ablation procedure is a
success, no further action is needed. If the procedure is not
successful, the clinician may opt to provide additional ablation
therapy at the same site and/or repeat the procedure of identifying
additional nerve targets (e.g, bilateral ablation) and providing
ablation therapy as described previously.
[0130] Ablation Catheter Embodiment
[0131] FIG. 18 schematically illustrates a distal end of a catheter
comprising a deployable balloon equipped with multiple surface
electrodes capable of transvenous stimulation and RF ablation of a
nerve from within a blood vessel. This device can be used in
conjunction with hemodynamic monitoring to locate the greater
splanchnic nerve, confirm a suitably safe and effective placement
of ablation electrodes, ablate the greater splanchnic nerve, and
confirm technical success of the ablation prior to withdrawing the
device from the body and closing the venous puncture. In this
embodiment the catheter shaft connects to a deployable structure
such as a balloon, which is shown placed in an azygos vein and
possibly distending the walls of the vein to bring ablation
electrodes and stimulation electrodes in apposition with the walls
of the vein. Application of a stimulation level current (energy)
systematically from stimulation electrodes positioned around the
balloon and in contact with the vein wall around its inner
circumference while observing physiologic response may be done to
identify where the greater splanchnic nerve is located along the
circumference of the vein. If the electric field generated by the
stimulation current from the electrode elicits the expected
hemodynamic response, the longitudinally corresponding ablation
electrode can be used to apply an ablation level of energy to
create a lesion.
[0132] Application of stimulation current to the electrode
following delivery of ablation energy while observing physiologic
response can be used to confirm technical success, wherein absence
or decrease of a physiologic response compared to the response
observed prior to ablation may indicate that the nerve was
successfully ablated.
[0133] In one embodiment, the catheter may be delivered
transvenously through the cardiovascular system, specifically to
the azygos vein via femoral access or internal jugular vein (IJV)
access. It is envisioned that the ablation element may be
positioned with or without the aid of a guide wire. When desired, a
hollow, multi-pole catheter can be used to maintain natural flow
levels within a blood vessel.
[0134] Stimulation elements used for confirmation of ablation
element's position or confirmation of technical or clinical success
are envisioned to contain one, two or more electrodes arranged in
series or arrays, distributed and spaced circumferentially or
longitudinally, which are chosen selectively to provide a
sufficient, optimal, or a situational amount of electrical
signaling. In these embodiments, the stimulation element may also
have a plurality of electrodes that may be used initially to map a
suitable location in an azygos or other suitable vein where the
greater splanchnic nerve runs within close proximity for the length
of 1-5 cm at a distance of about 1-5 millimeters, or crosses the
vein, sometimes about 2-3 millimeters from the vein wall, through
detecting a specific hemodynamic response to stimulation.
[0135] By way of example, the catheter and console system may
comprise a catheter 10 having multiple electrodes spaced along a
flexible shaft having a distal end region configured to be placed
in an intercostal vein of a patient. The console is configured to
generate and control delivery of ablation signals (high energy
electrical pulses) and electrical stimulation signals (low energy
electrical pulses). The low energy signals may include frequencies
in the range of 5-50 Hz and high energy signals include frequencies
in the range of 400-500 Hz. The low energy signal is selected to
stimulate nerves proximate to the active electrode and the high
energy signal is configured to ablate the nerves proximate to the
active electrode. The signals are applied to the electrodes on the
distal end region of the catheter. The console is capable of
selectively applying low and high levels of energy to each the
electrodes, such as by sequentially applying low energy pulses to
all of the electrodes and applying high energy pulses to selected
ones of the electrodes.
[0136] The console may be configured with a controller configured,
e.g., programmed, to select and thereby activate an electrode and
or group of electrodes (monopolar and/or bipolar) and; to select
delivery of high or low energy. The selection means for selecting
electrode and delivery can include a switch or program logic. The
console may include physiologic monitoring device or devices in
communication with the console, where the physiological monitoring
device may include sensors located on the catheter device,
elsewhere within the patient vasculature, and/or
non-invasively.
[0137] A computer controller in the console may execute software
and logic that include algorithms that facilitate analysis of
hemodynamic and physiologic values recorded from patient monitoring
device or devices in communication with the console. Examples of
hemodynamic and physiological parameters are pupil dilation,
increased sweating, increased heart rate, increased blood pressure,
increased mean arterial pressure and any combination thereof.
[0138] The algorithms may confirm the positioning of the electrodes
along the catheter in the intercostal vein with respect to the
target nerve by automatically detecting a change in at least one
selected hemodynamic or physiological parameter which occurs in
response to the activation of an electrode on the catheter by a
stimulation pulse. The algorithm may initially cause the
recordation of a baseline vale of the hemodynamic parameter.
Thereafter, algorithm causes stimulation pulse to be applied to the
intercostal vein by one or more of the electrodes on the catheter.
The stimulation pulse may have a current (I), a pulse width (pw), a
frequency (F) and a duty cycle (D) wherein I=0-10 mA, pw=100-1000
us, F=20-40 Hz, and D=50% pulsing between 20-60 s. As each
stimulation pulse is applied, the algorithm records the value of
the selected hemodynamic or physiological parameter. The
application of a stimulation pulse and recording the parameter
value resulting from the pulse may proceed in a sequence for each
of the electrodes on the catheter.
[0139] The recorded parameter values are used to select the
electrodes are to receive an ablation pulse. The selection may be
the electrode(s) corresponding to the largest change in the
parameter value from the baseline value. Further, the selection may
be to identify electrodes which, which applying the stimulation
pulse, caused the parameter value to exceed a certain threshold,
such as a twenty percent change (20%) from the baseline value.
[0140] To ensure a reliable parameter value, the stimulation pulse
may be applied several times, such as three by each of the
electrodes. The parameter value is recorded during each stimulation
pulse. The average of the parameter values for each of the
stimulation pulse applied to a specific electrode may be used as
the parameter value to select an electrode for the ablation pulse.
Also, a check may be made to the parameter values to conform that
are within a certain range, such as within ten percent of each
other. If any of the values are outside of the range, additional
stimulation pulses may be applied to determine the average value or
an alert may be generated by the console that is given to the
health care provider.
[0141] The algorithm followed by the computer controller may be
used to confirm a patient will experience the desired physiological
effect of ablation before delivering ablation therapy is performed
by an automated algorithmic process. Such an algorithm may include:
temporarily blocking the target nerve with a stimulation signal,
recording the physiologic response while the nerve is blocked, and
evaluating the physiologic response to determine if the patient
should undergo ablation of nerve by ablating the intercostal vein
near the nerve. Clinical effectiveness is determined by comparing
the recorded response to the desired physiologic response. The
desired response may be progressive reductions in pressures (e.g.,
MAP, PAP, and LVEDP).The target nerve may also be temporarily
blocked pharmacologically or cryogenically. If temporary blocking
does not achieve the desired effect, the physician may decide not
to proceed with ablation, select a different electrode
configuration on the catheter to apply a stimulation signal and
thereafter an ablation signal, or move rotationally or laterally
the catheter and its electrodes in the intercostal vein.
[0142] The algorithm executed by the computer controller may also
confirm the technical efficacy or success of the ablation
procedure. The confirmation steps would be after (post) the
ablation of the nerve via the intercostal vein. The conformation
steps may include electrical stimulation by the catheter to a
region of the intercostal vein the same as or proximal to the
location of the ablation. The patient's response (physiological or
hemodynamic) to the electrical stimulation is recorded and compared
to the response prior to ablation. If the comparison indicates an
attenuation or absence of a response, the algorithm will indicate
technical success of the ablation procedure.
[0143] If the comparison indicates an unsuccessful ablation
procedure, the physician or other health care provider may repeat
the ablation therapy at the same site and/or repeat the therapy
procedure for other nerve targets. Additional nerve targets could
include bilateral ablation.
[0144] The console may include a graphical user interface
configured to present information from the physiological signals
where the information is the physiological response following
(e.g., 5-60 seconds) the delivery of low and/or high energy and;
algorithms that compare the physiologic signals to data from memory
stored baseline values providing automated selection of appropriate
electrode configurations and/or the appropriate energy
delivery.
[0145] While certain forms of electrodes, or arrays/series of
electrodes have been illustrated and described herein, it is not to
be limited to the specific forms or arrangement of parts described
and shown.
[0146] Studies:
[0147] It is known that clinically beneficial effects can be
obtained in patients with heart failure by administering
pharmacological therapies, such as nitroglycerine, to cause
venodilation. These effects are immediate and pronounced in
magnitude to the point where they can lead to severe side effects
of low systemic blood pressure and poor vital organ perfusion.
Stimulation of the GSN results in a rapid and large increase in
blood pressure through a reduction in splanchnic vascular
compliance, for example as shown by the experiment illustrated by
FIG. 14. Thus, it was reasonable to be concerned that reduction in
GSN activity by resection or ablation of the GSN could lead to the
opposite effect, specifically to venodilation of the splanchnic
circulation, resulting in a large, abrupt reduction in blood
pressure and cardiac preload similar to that observed with
pharmacological therapy.
[0148] An animal experiment was conducted to examine the worst case
scenario, or total reduction in GSN activity, by cutting the GSN. A
sharp, immediate reduction in blood pressure was anticipated.
However, unexpectedly and counterintuitively, cutting of the GSN
instead resulted in a slow, progressive reduction in pressures with
unexpected beneficial changes in other hemodynamic measures.
[0149] Vascular capacitance can be increased in dogs with rapid
pacing- induced heart failure by surgical resection or equivalent
but less invasive percutaneous (through the chest wall) or
transvenous ablation of a left or right greater splanchnic nerve
resulting in profound improvement of cardiac function, pulmonary
artery blood pressure and other relevant hemodynamic parameters.
For the CHF patients such magnitude of changes can affect a number
of clinical outcomes including mortality, exercise capacity, need
for hospitalization and quality of life. While there may also be a
place for controlled or intermittent inhibition of GSN activity in
some patients, complete reduction in GSN activity may cause
physiological changes that can result in clinically significant
benefits in patients with heart failure and/or other diseases
associated with fluid overload without the immediate side effects
frequently seen with pharmacological therapy. Ablation of a nerve
caused by an ablation catheter is envisioned to impede or eliminate
signal transfer through a nerve similar to that caused by surgical
resection.
[0150] While at least one exemplary embodiment of the present
invention(s) is disclosed herein, it should be understood that
modifications, substitutions and alternatives may be apparent to
one of ordinary skill in the art and can be made without departing
from the scope of this disclosure. This disclosure is intended to
cover any adaptations or variations of the exemplary embodiment(s).
In addition, in this disclosure, the terms "comprise" or
"comprising" do not exclude other elements or steps, the terms "a"
or "one" do not exclude a plural number, and the term "or" means
either or both. Furthermore, characteristics or steps which have
been described may also be used in combination with other
characteristics or steps and in any order unless the disclosure or
context suggests otherwise. This disclosure hereby incorporates by
reference the complete disclosure of any patent or application from
which it claims benefit or priority.
* * * * *